The Kaposi?s Sarcoma Herpesvirus (KSHV) is the causative agent of Kaposi?s Sarcoma (KS) and is associated with primary effusion lymphoma (PEL) and multicentric Castleman?s disease (MCD) as well as two inflammatory diseases: KSHV inflammatory cytokine syndrome and immune reconstitution syndrome-KS. KSHV-associated cancers are primarily associated with genes expressed during the latent phase of the viral lifecycle that allow the infected cell to survive despite harboring a viral genome. The major lytic switch of the virus, RTA, interacts with the cellular machinery to co-opt the host ubiquitin proteasome system to evade the immune response as well as activate the program of lytic replication. Here we propose to identify novel targets of RTA through the analysis of cellular ubiquitinated proteins, or ubiquitinated proteome. The results of this analysis will increase our knowledge of mechanisms governing the transition from latency to lytic replication and have potential clinical implications for development of novel therapeutics.